Review
Cell Biology
Amit S. Joshi
Summary: Peroxisomes are vital organelles in cells, generated and maintained through membrane contacts with other organelles, playing a crucial role in normal cellular function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jose M. Horcas-Nieto, Christian J. Versloot, Miriam Langelaar-Makkinje, Albert Gerding, Tjasso Blokzijl, Mirjam H. Koster, Mirjam Baanstra, Ingrid A. Martini, Robert P. Coppes, Celine Bourdon, Sven C. D. van Ijzendoorn, Peter Kim, Robert H. J. Bandsma, Barbara M. Bakker
Summary: Hospitalized children with severe malnutrition often suffer from hepatic and intestinal dysfunction, leading to high mortality rates. Our study has established organoid models of severe malnutrition in the liver and intestine, which recapitulate the expected functional changes and protein alterations seen in these organs. By re-supplementing amino acids or using specific drugs, we observed partial recovery of organoid function. These organoid models serve as valuable tools for understanding the underlying mechanisms and testing potential treatments for intestinal and hepatic dysfunction in severe malnutrition.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Lea P. Wilhelm, Juan Zapata-Munoz, Beatriz Villarejo-Zori, Stephanie Pellegrin, Catarina Martins Freire, Ashley M. Toye, Patricia Boya, Ian G. Ganley
Summary: This study reveals that both mitophagy and pexophagy are activated upon iron chelation in a BNIP3L/NIX-dependent manner. The NIX protein, known as a mitophagy receptor, is also found to localize to peroxisomes and drive pexophagy independently.
Article
Biochemistry & Molecular Biology
Minghui Wang, Yanqing Ding, Yuehuai Hu, Zeyu Li, Wenwei Luo, Peiqing Liu, Zhuoming Li
Summary: The study reveals a novel mechanism of SIRT3 in protecting against pathological cardiac hypertrophy by maintaining the interaction between peroxisomes and mitochondria through PEX5. It shows that SIRT3 preserves PEX5 expression, improving mitochondrial function and alleviating peroxisomal abnormalities. PEX5 deficiency leads to mitochondrial impairment, emphasizing the importance of PEX5 in regulating the peroxisome-mitochondria interplay. These findings provide new insights into the role of SIRT3 in mitochondrial regulation via interorganelle communication in cardiomyocytes.
Article
Cell Biology
Clarissa Braccia, Josie A. Christopher, Oliver M. Crook, Lisa M. Breckels, Rayner M. L. Queiroz, Nara Liessi, Valeria Tomati, Valeria Capurro, Tiziano Bandiera, Simona Baldassari, Nicoletta Pedemonte, Kathryn S. Lilley, Andrea Armirotti
Summary: This study investigates the impact of pharmacological rescue treatment on the proteome of a CF model. The results suggest that VX-809 treatment induces extensive structural and functional remodeling of mitochondria and peroxisomes. These findings are important for further understanding the therapeutic mechanisms and drug research of CF.
Article
Cell Biology
Lea Schuermanns, Andrea Hamann, Heinz D. Osiewacz
Summary: The maintenance of cellular homeostasis is crucial for preventing the degeneration of biological systems. In this study, the researchers found that an oleic acid diet can extend the lifespan of cells by restoring membrane trafficking and altering mitochondrial respiratory chain.
Article
Cardiac & Cardiovascular Systems
Felipe Kazmirczak, Lynn M. Hartweck, Neal T. Vogel, Jenna B. Mendelson, Anna K. Park, Rashmi M. Raveendran, Jin O-Uchi, Bong Sook Jhun, Sasha Z. Prisco, Kurt W. Prins
Summary: Intermittent fasting (IF) extends life span through pleotropic mechanisms, with adenosine monophosphate-activated protein kinase (AMPK) playing a crucial role. AMPK enhances lipid metabolism and modulates microtubule dynamics. Dysregulation of these pathways leads to right ventricular (RV) failure in pulmonary arterial hypertension patients. In rodent models of pulmonary arterial hypertension, IF activates RV AMPK, restoring mitochondrial and peroxisomal morphology and regulating lipid metabolism proteins. Additionally, IF increases electron transport chain protein levels and activity in the right ventricle. RV function measured by echocardiography and hemodynamics correlates positively with fatty acid oxidation and electron transport chain protein levels. IF also normalizes transverse tubule structure by reducing microtubule density.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2023)
Article
Plant Sciences
Jaideep Mathur, Olivia Friesen Kroeker, Mariann Lobbezoo, Neeta Mathur
Summary: The optimal functioning of plant cells depends on efficient exchange between organelles, which may be facilitated by increased proximity and involvement of the endoplasmic reticulum (ER). This study found that under normal conditions, direct physical contact between organelles is not observed, but all organelles maintain close connectivity with the ER. Increased proximity between organelles occurs in response to stress, but the ER remains sandwiched between them. This provides evidence for the ER acting as a mediator in interactions between other organelles.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Food Science & Technology
Song Gao, Yueyue Liu, Longteng Zhang, Yuqing Tan, Bo Li, Hui Hong, Yongkang Luo
Summary: The addition of NaCl is closely related to the oxidation of meat, and mitochondria play a key role in the oxidation process of proteins. This study found that increasing concentrations of NaCl caused higher levels of oxidation in bighead carp fillets by affecting mitochondrial membrane potential and enzyme activity. Notably, 2.0 M NaCl was found to promote lipid or protein oxidation by disrupting mitochondrial membrane structure and influencing peroxisome activity.
FOOD RESEARCH INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Zhuang Hao, Zhen Li, Jinjin Huo, Jiandong Li, Fenghua Liu, Peng Yin
Summary: The study demonstrated that Chinese wolfberry and Astragalus extract had a significant effect on the antioxidant capacity of Tibetan pig liver, enhancing antioxidant ability through regulation of oxidative stress-related genes and signaling pathways. The findings suggest a potential mechanism for improving liver health in pigs.
Review
Cell Biology
Chenxing Jiang, Tomohiko Okazaki
Summary: Peroxisomes are organelles that play a role in various metabolic pathways. Their biogenesis is controlled by a group of proteins, and mutations in these proteins can cause metabolic disorders. Recent research has shown that peroxisomes are involved in regulating cell apoptosis and fusion processes, and disruption of these processes may be related to the pathogenesis of specific diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Esther Nuebel, Jeffrey T. Morgan, Sarah Fogarty, Jacob M. Winter, Sandra Lettlova, Jordan A. Berg, Yu-Chan Chen, Chelsea U. Kidwell, J. Alan Maschek, Katie J. Clowers, Catherine Argyriou, Lingxiao Chen, Ilka Wittig, James E. Cox, Minna Roh-Johnson, Nancy Braverman, Joshua Bonkowsky, Steven P. Gygi, Jared Rutter
Summary: Peroxisomal biogenesis disorders (PBDs) are genetic disorders characterized by impaired peroxisome biogenesis and metabolism, with the most severe form being Zellweger spectrum disorder (ZSD) which can lead to mitochondrial dysfunction. Research suggests that abnormal peroxisomal protein localization may play a crucial role in the devastating mitochondrial morphological and metabolic phenotypes observed in ZSD.
Article
Cell Biology
Tina A. Schrader, Ruth E. Carmichael, Markus Islinger, Joseph L. Costello, Christian Hacker, Nina A. Bonekamp, Jochen H. Weishaupt, Peter M. Andersen, Michael Schrader
Summary: This study reveals a novel pathway for peroxisome division and identifies the role of FIS1 in peroxisome division.
JOURNAL OF CELL SCIENCE
(2022)
Article
Environmental Sciences
Christopher Powers, Fatma Gomaa, Elizabeth B. Billings, Daniel R. Utter, David J. Beaudoin, Virginia P. Edgcomb, Colleen M. Hansel, Scott D. Wankel, Helena L. Filipsson, Ying Zhang, Joan M. Bernhard
Summary: This study used transcriptomics and metatranscriptomics to investigate the gene expression differences of two benthic foraminifera species thriving in oxygen-depleted marine sediments, revealing their utilization of adaptable mitochondrial and peroxisomal metabolism to adapt to varying oxygen levels and chemical environments.
FRONTIERS IN MARINE SCIENCE
(2022)
Article
Evolutionary Biology
Emma Collington, Briallen Lobb, Nooran Abu Mazen, Andrew C. Doxey, D. Moira Glerum
Summary: By analyzing 155 helminth genomes, it was found that 52% of helminth species lack essential cytochrome c oxidase genes and 42% of species have a significant absence of essential peroxisomal protein-coding genes. These results indicate significant differences in oxygen utilization between parasitic and nonparasitic helminths, offering a potential pathway for the development of anthelmintic agents.
GENOME BIOLOGY AND EVOLUTION
(2023)
Article
Multidisciplinary Sciences
Noa Dahan, Yury S. Bykov, Elizabeth A. Boydston, Amir Fadel, Zohar Gazi, Hodaya Hochberg-Laufer, James Martenson, Vlad Denic, Yaron Shav-Tal, Jonathan S. Weissman, Naama Aviram, Einat Zalckvar, Maya Schuldiner
Summary: This study discovered that translation of specific peroxisomal membrane proteins (PMPs) occurs on the surface of peroxisomes in yeast, similar to chloroplasts, mitochondria, and the endoplasmic reticulum. This localized translation process ensures the correct insertion of hydrophobic proteins into the peroxisomal membrane. Proper targeting of PMP transcripts to peroxisomes is crucial for cellular and peroxisomal function, highlighting the importance of localized translation in cellular physiology.
Article
Cell Biology
Yotam David, Ines Gomes Castro, Eden Yifrach, Chen Bibi, Enas Katawi, Dekel Yahav Har-Shai, Sagie Brodsky, Naama Barkai, Tommer Ravid, Miriam Eisenstein, Shmuel Pietrokovski, Maya Schuldiner, Einat Zalckvar
Summary: Peroxisomes are essential for human health and survival as they host important metabolic enzymes. By using a high-throughput screen in yeast, researchers discovered 18 previously unidentified peroxisomal proteins and investigated their dependence on metabolic and targeting factors for peroxisomal localization. One newly identified protein, Pls1, was found to affect the lysine biosynthesis pathway.
Article
Cell Biology
Daniel D. Bisinski, Ines Gomes Castro, Muriel Mari, Stefan Walter, Florian Froehlich, Maya Schuldiner, Ayelen Gonzalez Montoro
Summary: Membrane contact sites are specialized platforms between organelles that facilitate metabolite exchange and influence dynamics. This study identifies a novel protein, Cvm1, that forms multiple contact sites in the yeast vacuole and plays a crucial role in sphingolipid homeostasis.
JOURNAL OF CELL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Einat Zalckvar, Maya Schuldiner
Summary: Metabolism is emerging as a central influencer of multiple disease states in humans, and the decreased function of peroxisomes is linked to various common diseases. However, research on the mechanisms underlying the contributions of peroxisomes to these diseases is still limited.
Article
Biochemistry & Molecular Biology
Sven Fischer, Jerome Buergi, Shiran Gabay-Maskit, Renate Maier, Thomas Mastalski, Eden Yifrach, Agnieszka Obarska-Kosinska, Markus Rudowitz, Ralf Erdmann, Harald W. Platta, Matthias Wilmanns, Maya Schuldiner, Einat Zalckvar, Silke Oeljeklaus, Friedel Drepper, Bettina Warscheid
Summary: This study identifies a novel Pex5p phosphorylation-dependent mechanism for regulating the import of PTS1-proteins into peroxisomes. The phosphorylation process affects the binding affinity between Pex5p and PTS1-proteins, thereby impacting their import into peroxisomes. These findings suggest that posttranslational modifications can function in fine-tuning the peroxisomal protein composition and cellular metabolism.
BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Eden Yifrach, Markus Rudowitz, Luis Daniel Cruz-Zaragoza, Asa Tirosh, Zohar Gazi, Yoav Peleg, Markus Kunze, Miriam Eisenstein, Wolfgang Schliebs, Maya Schuldiner, Ralf Erdmann, Einat Zalckvar
Summary: This study reveals that the targeting specificity of peroxisomal proteins in yeast is mainly determined by the hydrophobic nature of the amino acid preceding the PTS1 signal. Structural modeling shows differences in surface hydrophobicity of the PTS1-binding cavities of the two factors. This work elucidates the mechanism by which targeting specificity is achieved, enabling dynamic rewiring of the peroxisomal proteome in response to changing metabolic needs.
BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Emma J. Fenech, Nir Cohen, Meital Kupervaser, Zohar Gazi, Maya Schuldiner
Summary: Identification of stable and transient protein interactions is crucial for understanding protein function and regulation. However, capturing transient interactions is challenging, especially in model organisms like Saccharomyces cerevisiae. In this study, the researchers optimized biotin-ligation methodologies in yeast and developed a technique called ABOLISH to downregulate endogenous biotinylation. They also generated five full-genome collections of strains to enable systematic probing of both stable and transient interactions. This comprehensive toolkit allows for functional interactomics of the entire yeast proteome.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Shiladitya Chattopadhyay, Jose Garcia-Martinez, Gal Haimovich, Jonathan Fischer, Aya Khwaja, Oren Barkai, Silvia Gabriela Chuartzman, Maya Schuldiner, Ron Elran, Miriam Rosenberg, Shira Urim, Shubham Deshmukh, Katherine E. Bohnsack, Markus T. Bohnsack, Jose E. Perez-Ortin, Mordechai Choder
Summary: This study reveals the crucial role of nucleocytoplasmic shuttling of yeast mRNA decay factors in regulating both transcription and mRNA decay. The shuttling process is controlled by decaying RNA and is essential for coping with environmental changes.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Renate L. M. Jansen, Marco van den Noort, Arjen M. Krikken, Chen Bibi, Astrid Boehm, Maya Schuldiner, Einat Zalckvar, Ida J. van der Klei
Summary: The mechanism of peroxisomal membrane protein targeting remains poorly understood, with only two proteins believed to be involved and no consensus targeting sequence. Pex19 is thought to bind these proteins in the cytosol and is then recruited by Pex3 at the peroxisomal surface, but how the protein is inserted is still unknown. This study found that Pxa1, a peroxisomal ABC transporter, requires both Pex3 and Pex19 for sorting, suggesting the existence of multiple sorting pathways.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Nir Cohen, Naama Aviram, Maya Schuldiner
Summary: This study presents a novel approach called Cel-lctiv for systematically comparing stable or transient protein-protein interactions (PPIs) between two yeast proteins. The approach utilizes high-throughput pairwise proximity biotin ligation to compare PPIs systematically and in vivo. Using homologous translocation pores Sec61 and Ssh1 as a proof of concept, the study demonstrates how Cel-lctiv can uncover substrate specificity and determine specificity determinants for protein interactions, even in highly homologous proteins.
Article
Cell Biology
Maayan Mark, Ofir Klein, Yu Zhang, Koyeli Das, Adi Elbaz, Reut Noa Hazan, Michal Lichtenstein, Norbert Lehming, Maya Schuldiner, Ophry Pines
Summary: Dual localization refers to proteins being localized to multiple compartments within a cell. In this study, the authors identified 280 new protein candidates that have an eclipsed distribution to mitochondria, meaning their main activity is outside mitochondria but they are also present at low levels within mitochondria. The researchers focused on a particular protein family, Triose-phosphate DeHydrogenases, and showed that their eclipsed distribution in mitochondria is important for mitochondrial activity. This work provides insights into the deliberate eclipsed localization, targeting, and function of proteins in mitochondria, and expands our understanding of mitochondrial function in health and disease.
Article
Biochemistry & Molecular Biology
Lakhan Ekal, Abdulaziz M. S. Alqahtani, Maya Schuldiner, Einat Zalckvar, Ewald H. Hettema, Kathryn R. Ayscough
Summary: Membrane-bound organelles are crucial for cellular metabolism in eukaryotes, and the actin cytoskeleton plays an important role in organelle transport. Studies in yeast have identified the key factors involved in organelle inheritance, but the regulation of organelle transport in yeast is still poorly understood.